Determining Endoscopic Treatment Response in Ulcerative Colitis and Crohn’s Disease using the Win Probability Approach

Lead Investigator: Vipul Jairath, Alimentiv Inc.
Title of Proposal Research: Determining Endoscopic Treatment Response in Ulcerative Colitis and Crohn’s Disease using the Win Probability Approach
Vivli Data Request: 9417
Funding Source: Alimentiv is providing funding in the form of resources to conduct the analysis. Alimentiv is a contract research organization that uses the profits from delivery of commercial services to reinvest in academic research that aligns with its partners shared purpose to accelerate drug discovery.
Potential Conflicts of Interest: Dr. Jairath reports: Received consulting fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pendopharm, Pfizer, Roche, Sandoz, Takeda, Topivert; speaker’s fees from, Abbvie, Ferring, Janssen, Pfizer Shire, Takeda. The research outlined in this study is not receiving funding from any of the outlined companies with the exception of Alimentiv Inc which is the sponsor and funder of this study. Alimentiv is not receiving any external funding for the conduct of this project, to minimize any influence on the planning, conduct or interpretation of outcomes. Full disclosure of all conflicts of interest will be included in any public disclosures. Any changes to conflicts of interest by the research team will be evaluated and reported to Vivli and YODA.
Dr. Guangyong Zou reports: Employee of Alimentiv Inc. Alimentiv is not receiving any external funding for the conduct of this project, to minimize any influence on the planning, conduct or interpretation of outcomes. Full disclosure of all conflicts of interest will be included in any public disclosures. Any changes to conflicts of interest by the research team will be evaluated and reported to Vivli and YODA.
Dr. Christopher Ma reports: Christopher Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Takeda; royalties from Springer Publishing; research support from Ferring, Pfizer.
Dr. Farzaana Ali reports: Farzaana Ali owns stock with the company AbbVie. The research outlined in this study is not receiving funding from any of the outlined companies with the exception of Alimentiv Inc which is the sponsor and funder of this study.

Summary of the Proposed Research:

Affecting approximately 3 million Americans (Dahlhamer et al., 2016), inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and Ulcerative Colitis (US) are conditions where the body’s immune system attacks the digestive system and causes inflammation of the bowel leading to abdominal pain, bloody stools, and diarrhea. In CD, inflammation can occur anywhere in the digestive tract from the mouth to the anus, whereas inflammation is primarily in the large intestine in UC.

Biologic and advanced small molecule therapies are 2 common medication classes for the treatment of patients with moderate-to-severe IBD. Biologics are medications made from living organisms based on a protein naturally made by the body. Advanced small molecules are chemicals that are smaller and simpler in structure than biologics.

An important goal of treatment is to heal the lining of the bowel, which is seen using imaging techniques where a flexible tube with a camera on the end is used to view the digestive tract (endoscopy). Trained experts can view endoscopic images/videos and measure IBD disease activity. In UC, disease activity is measured using the Mayo Endoscopic subscore (MES), which is a 4-level score (0=normal, 1=mild, 2=moderate, 3=severe), whereas, in CD, disease activity is measured using the Simple Endoscopic Score for CD, which is an instrument consisting of multi-level scoring across multiple bowel segments.

Historically, endoscopic data in IBD studies have used subjective thresholds to define outcomes, such as whether a patient shows endoscopic improvement (response), endoscopic remission (no disease), or not. The percentage of patients in each treatment group in a trial who meet these outcomes are then compared by conventional methods for binary outcomes – meaning that having met or not met the outcome.

However, there are problems to this approach. First, using this approach does not account for all study data. For example, if remission is defined by an MES score of 0 or 1, then this analysis treats all patients with MES scores of 0 or 1 as the same, and MES scores of 2 or 3 as the same, even if there are differences in these patients. Second, definitions of endoscopic outcomes (remission versus no remission) have changed over time, making it hard to compare different studies to each other.

In this study, we propose analyzing IBD data without categorizing the disease scores into binary outcomes. Our goal is to account for the type of data captured by endoscopy, to compare biologic and small molecule therapies and to examine which is best for improving endoscopic disease activity. We will reduce potential bias and improve accuracy by accounting for a patient’s disease activity before treatment.

Requested Studies:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Infliximab in Chinese Subjects With Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT01551290
Sponsor ID: CR018769

A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00036439
Sponsor ID: CR004777

A Multi-Center, Randomized, Double-Blind, Placebo-controlled Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis.
Data Contributor: AbbVie
Study ID: NCT00853099
Sponsor ID: M10-447

A Multicenter, Randomized, Double-blind Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: AbbVie
Study ID: NCT00385736
Sponsor ID: M06-826

A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: AbbVie
Study ID: NCT00408629
Sponsor ID: M06-827

A Phase 3 Multicenter, Placebo-controlled, Double-blind, Randomized-withdrawal Study to Evaluate the Safety and Efficacy of Golimumab Maintenance Therapy, Administered Subcutaneously, in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT01863771
Sponsor ID: CR100937

A Phase 3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Maintenance Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00488631
Sponsor ID: CR014179

A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Intravenously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00488774
Sponsor ID: CR014188

A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00487539
Sponsor ID: CR014176

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

Phase III, Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Study to Examine the Efficacy, Safety, and Pharmacokinetics of Intravenous MLN0002 (300 mg) Infusion in Induction and Maintenance Therapy in Japanese Patients With Moderately or Severely Active Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT02039505
Sponsor ID: MLN0002/CCT-101